Single strand annealing mathematical model for double strand break repair

Abstract

Abstract: Background: In this work we present, for the first, a mechanistic mathematical model for single strand annealing (SSA) one of the three important double strand breaks (DSB) repair pathway. For this purpose, we predict the rate constants, which have not yet been measured experimentally, for the proteins involved in the repair. To maintain genome stability, DNA DSB are repaired by three main pathways, NHEJ (non-homologous end joining), HR (homologous recombination), and SSA. SSA is a compensating pathway for both HR and NHEJ. The three pathways are distinct in repair efficiency and fidelity. The SSA repair process is non-conservative which causes genome translocation.Methods: We employed a biochemical reaction rate model to investigate mechanistically the SSA repair pathway. The model resulted in a set of nonlinear differential equations which were solved numerically.Results: The reaction rates of the model were estimated by comparing the modelling results with chicken cell line (DT40), and mouse embryo fibroblast cell line (MEF) dose-equivalent unrepaired DSB (Deq) data after irradiation with 20 Gy X-rays. The model successfully predicted DSB repair of DT40 cell line irradiated with 80 Gy X-rays. The model was also employed to investigate dose rate effects on repair efficiency.